RESUMO
Ubiquitin-conjugating enzyme E2S (UBE2S) is involved in protein degradation and signal transduction, but its function in the development of melanoma is unclear. We focused on the role of UBE2S in melanoma development both in vitro and in vivo. UBE2S was overexpressed in malignant melanoma cells and tissues, and UBE2S expression was significantly different between tumor node metastasis staging T4 and T1/T2/T3. We designed UBE2S short hairpin RNA (shUBE2S) and transfected it into A375, SK-MEL-28, and MUM-2B cells using lentivirus. By whole-genome filtering, 247 genes and 265 genes were upregulated and downregulated, respectively, in shUBE2S-treated melanoma; these genes were mainly involved in immune reactions, apoptosis, DNA damage repair, and cell movement. The proliferation of melanoma cells was inhibited, apoptosis was increased, and cell cycle was arrested in G1/S in shUBE2S-treated melanoma. Expression of epithelial to mesenchymal transition-related proteins was significantly suppressed, and tumor growth was also suppressed in shUBE2S BALB/C nude mice. shUBE2S treatment may cause cell cycle arrest in G1/S phase, inhibit proliferation, induce apoptosis, and suppress tumor growth through DNA damage repair, epithelial to mesenchymal transition inhibition, protein kinase B-mTOR pathway, NF-κB signaling, and immune reactions, which provides a comprehensive understanding of the role of UBE2S in melanoma development and the need for advanced clinical research into UBE2S.
Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Neoplasias Cutâneas/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Melanoma/patologia , Camundongos , Pessoa de Meia-Idade , Transdução de Sinais/genética , Neoplasias Cutâneas/patologia , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitinação , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Reflectance confocal microscopy (RCM), a noninvasive, real-time technique of computed tomography, has been widely used for pigmentary, inflammatory, and tumor diseases of the skin. AIM: Our main purpose was to analyze the consistency between pathological and RCM characteristics of early-stage mycosis fungoides (MF) and the utility of RCM in the diagnosis of early-stage MF. METHODS: According to the RCM features of MF in the early stage, the biopsy sites of 40 cases of suspected MF and 20 cases of chronic inflammatory skin diseases clinically were preliminarily located. Histopathologic and immunohistochemical examinations were performed to make a diagnosis based on the diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas. RESULTS: Among the 60 patients observed, there were 12 confirming cases of MF, 14 suspecting cases, 6 not completely excluding cases, and 28 eliminating cases according to the diagnostic algorithm, as well as characteristics of RCM were typical in 8 cases, suspected in 16 cases, not excluded in 3 cases, and excluded in 33 cases. The kappa value was 0.769 (P < .01), which means there is a strong consistency between the classification by RCM and the diagnosis algorithm. MF in patch stage and plaque stage (IA to IIB) has typical characteristics of RCM, respectively. CONCLUSIONS: RCM can be used as an objective and convenient auxiliary means to diagnose early-stage MF and may be included as part of the diagnostic algorithm of early-stage MF.